Digital polymerase chain reaction (dPCR) is a refinement of conventional PCR methods that can be used to directly quantify and clonally amplify nucleic acids. Conventional PCR assumes that amplification is exponential. Therefore, nucleic acids may be quantified by comparing the number of amplification cycles and amount of PCR end-product to those of a reference sample. However, many factors complicate this calculation, creating uncertainties and inaccuracies, including: non-exponential amplification of initial cycles, amplification plateaus, low initial concentrations of target nucleic acid molecules, and differences in amplification efficiency between target and reference sequences. Digital PCR is designed to quantitate target nucleic acid sequences by partitioning the PCR reaction into a sufficient number of reaction subvolumes so that the target is in limiting dilution, i.e., producing a sufficient number of reaction subvolumes with zero target copies so as to allow the application of Poisson statistics. Quantitation is achieved by running the reaction through a fixed number of cycles, sufficient to suitably amplify 1 copy to a detectable response and then counting the number of reactive and non-reactive subvolumes. Quantitation is based on application of Poisson statistics, notably using the number of non-reactive subvolumes to establish the number of initial copies that were distributed across all the reaction subvolumes. However, digital PCR typically requires that a sample be partitioned into many subvolumes such that a significant number of these subvolumes contain zero target nucleic acid molecules. Problems for quantitation by digital PCR arise when the concentration of nucleic acid molecules is too high such that the number of subvolumes containing zero target is nonexistent or is too low to apply Poisson statistics. Conventional dPCR is impractical for applications where the dynamic range is large, e.g., >106 copies per reaction. In high titer samples, even after dividing a sample into a large number of partitions, it may not be possible to create a population of zero target subvolumes without creating an impractically high number of subvolumes. What are needed are methods to accurately quantitate samples using the digital PCR format in which partitions contain as many as 10, 100, or more target molecules.